Neonatal oral administration of DiaPep277, combined with hydrolysed casein diet, protects against Type 1 diabetes in BB-DP rats. An experimental study

Abstract

Aims/hypothesis. Environmental factors such as diet and bacterial antigens play an important role in the onset of Type 1 diabetes. Different self-antigens are suggested to play a role in the development of diabetes. Antibodies against the 60-kDa heat shock protein 60, which have a high homology to bacterial heat shock protein 65, have been found in the circulation at the onset of diabetes in humans and in pre-diabetic NOD-mice. One of the immunodominant epitopes in autoimmune diabetes is p277, a specific peptide of human heat shock protein 60 corresponding to positions 437-460. In this study we investigated whether neonatal oral administration of DiaPep277 (a synthetic peptide analogue of p277) affected the development of diabetes in the BioBreeding-Diabetes Prone (BB-DP) rat, and whether this could potentiate the effect of a protective hydrolysed casein-diet.Methods. BB-DP rats were orally inoculated once per day with placebo or DiaPep277 at days 4, 5, 6 and 7 of life. At the age of 21 days rats were weaned on to a conventional, cereal-based diet or on to the hydrolysed casein-diet. Results. The development of diabetes in animals receiving DiaPep277 in combination with the hydrolysed casein-diet was delayed by 17 days, and a relative reduction of the incidence by 64% was seen. Nondiabetic animals did not show any sign of insulitis. Conclusions/interpretation. Short-term neonatal feeding with p277 in early life, combined with diet adaptation, appears to provide a procedure to significantly reduce the development of Type 1 diabetes in later life.Keywords BB-DP rat · DiaPep277 · Hydrolysed casein diet · Neonatal · Oral administration · Type 1 diabetes Abbreviations: BB-DP, BioBreeding diabetes-prone · HC, hydrolysed casein · hsp60/65, heat shock protein 60/65 · ICA-69, islet cell antigen 69 · NOD, non-obese diabetic

Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes?

“…The increasing prevalence of food allergies in Western societies has led to the hypothesis that increased hygienic conditions throughout life can disturb normal tolerance induction to otherwise harmless food proteins and other (inhaled) antigens. Previous studies have shown that modulation of antigen exposure early in life can change the diabetes incidence in BB-DP rats [5,6]. Furthermore, the antistaphylococcal drug fusidin was able to decrease the diabetes incidence in BB-DP rats [7].…”

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

“…In BBDP rats, gliadin exposure is accompanied by increased intestinal permeability (115) and zonulin release (168,173), presumably allowing food antigens to come in contact with the underlying lamina propria. Feeding NOD mice and BBDP rats a gluten-free hydrolyzed casein diet resulted in a delay and reduction of T1D development (27,28,144,167). Interestingly, in these animal models of T1D, the moment of exposure to wheat proteins was shown to be important for the development of T1D.…”

Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse

“…Furthermore, previous findings suggest that immunomodulators of the neonatal gut immune system play a particular role in controlling diabetes development [19,20]. According to the hygiene hypothesis, decreased bacterial exposure in early life leads to defective Treg cell induction, and is thus responsible for an autoimmune initiation of inflammatory cytokine production [2,21,22].…”